Neurodevelopmental outcomes in preterm or low birth weight infants with germinal matrix-intraventricular hemorrhage: a meta-analysis

Background This meta-analysis aimed to identify the near- and long-term neurodevelopmental prognoses of preterm or low birth weight (LBW) infants with different severities of intraventricular hemorrhage (IVH). Methods Four databases were searched for observational studies that were qualified using the Newcastle-Ottawa Scale. Results 37 studies involving 32,370 children were included. Compared to children without IVH, children with mild IVH had higher incidences of neurodevelopmental impairment (NDI), cerebral palsy (CP), motor/cognitive delay, hearing impairment and visual impairment, as well as lower scores of the mental development index (MDI) and psychomotor development (PDI). Moreover, compared to mild IVH, severe IVH increased susceptibilities of children to NDI, motor delay, CP, hearing impairment and visual impairment, with worse performances in MDI, PDI, motor score and IQ. Mild IVH was not associated with seizures or epilepsy. Conclusions Adverse neurodevelopmental outcomes positively associated with the occurrence and severity of IVH in preterm or LBW infants, providing evidence for counseling and further decisions regarding early therapeutic interventions. Impact Adverse neurodevelopmental outcomes later in life were closely associated with the occurrence and severity of IVH in preterm or LBW infants. Our results highlight the importance to make prediction of the neurodevelopmental outcomes of children born preterm or LBW with a history of IVH, which will guide affected parents when their children need clinical interventions to reach the full potential. We emphasize the importance of identifying specific developmental delays that may exist in children with IVH, providing detailed information for the development of comprehensive intervention measures.


Search strategy of Cochrane Library
No.

Eligibility criteria 5
Specify the inclusion and exclusion criteria for the review and how studies were grouped for the syntheses.Pgs.7-9 Information sources 6 Specify all databases, registers, websites, organisations, reference lists and other sources searched or consulted to identify studies.
Specify the date when each source was last searched or consulted.

Pg. 7
Search strategy 7 Present the full search strategies for all databases, registers and websites, including any filters and limits used.Pg. 7 Selection process 8 Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process.
Pg. 9 Data collection process 9 Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process.

Data items 10a
List and define all outcomes for which data were sought.Specify whether all results that were compatible with each outcome domain in each study were sought (e.g. for all measures, time points, analyses), and if not, the methods used to decide which results to collect.

Pgs. 8 and 9 10b
List and define all other variables for which data were sought (e.g.participant and intervention characteristics, funding sources).
Describe any assumptions made about any missing or unclear information.
et al., 2018 [30]   Reubsaet, P.et al., 2017 [9]   Was the Case Definition Figure S1.Sensitivity analysis for the outcome of NDI.(a) Comparison results between children with mild IVH vs. without IVH.(b) Comparison results between children with severe IVH vs. mild IVH.

Figure S2 .
Figure S2.Sensitivity analysis for the outcome of MDI and PDI.(a) Mean difference of MDI for children with mild IVH vs. children without IVH.(b) Mean difference of MDI for children with severe IVH vs. children with mild IVH.(c) Mean difference of PDI for children with mild IVH vs. children without IVH.(d) Mean difference of PDI for children with severe IVH vs. children with mild IVH.(e) OR for the outcome of MDI scored below 70 for mild IVH vs. without IVH.(f) OR for the outcome of PDI scored below 70 for mild IVH vs. without IVH.

Figure S3 .
Figure S3.Sensitivity analysis for the outcome of motor scores.(a) Mean difference of motor scores for children with severe IVH vs. children with mild IVH.(b) Mean difference of motor scores for children with mild IVH vs. children without IVH.(c) OR for the outcome of motor delay comparison between mild IVH vs. without IVH.(d) OR for the outcome of motor delay comparison between severe IVH vs. mild IVH.

Figure S5 .
Figure S5.Sensitivity analysis for the outcome of hearing impairment and visual impairment.(a) OR for the outcome of hearing impairment comparison between mild IVH vs. without IVH.(b) OR for the outcome of hearing impairment comparison between severe IVH vs. mild IVH.(c) OR for the outcome of visual impairment comparison between mild IVH vs. without IVH.(d) OR for the outcome of visual impairment comparison between severe IVH vs. mild IVH.

Figure S6 .
Figure S6.Sensitivity analysis for the outcome of CP and seizure events or epilepsy.(a) OR for the

Figure S7 .
Figure S7.Publication bias plot of CP, visual impairment, NDI and hearing impairment.(a) CP for the comparison between children with mild IVH vs. without IVH.(b) CP for the comparison between children with severe IVH vs. mild IVH.(c) Visual impairment for the comparison between children with mild IVH vs. without IVH.(d) Visual impairment for the comparison between children with severe IVH vs. mild IVH.(e) NDI for the comparison between children with mild IVH vs. without IVH.(f) Hearing impairment for the comparison between children with mild IVH vs. without IVH.

Figure S8 .
Figure S8.Trim method to evaluate the impact of publication bias on NDI.

Table S2 . Baseline characteristics of the 37 studies for meta-analysis
all statistical syntheses conducted.If meta-analysis was done, present for each the summary estimate and its precision (e.g.confidence/credible interval) and measures of statistical heterogeneity.If comparing groups, describe the direction of the effect.
Synthesis methods 13aDescribe the processes used to decide which studies were eligible for each synthesis (e.g.tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item #5)).Pg. 10 13bDescribe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data Pg.10-11RESULTSStudy selection 16aDescribe the of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram.Pg.12 16bCite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded.the following are publicly available and where they can be found: template data collection forms; data extracted from included studies; data used for all analyses; analytic code; any other materials used in the review.